title: Synthesis and antitumor activities of novel thiourea α-aminophosphonates from dehydroabietic acid.
abstract: A series of novel thiourea α-aminophosphonate derivatives containing DHA structure was designed and synthesized as antitumor agents. Their inhibitory activities against the NCI-H460 (lung), A549 (lung adenocarcinoma), HepG2 (liver) and SKOV3 (ovarian) human cancer cell lines were estimated using MTT assay in vitro. The screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which indicated that the compound can induce cell apoptosis in A549 cells.
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Chemical Engineering of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
authors.forename: Xiao-Chao
authors.initials: XC
authors.lastname: Huang
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Pan
authors.forename: Gui-Yang
authors.initials: GY
authors.lastname: Yao
authors.forename: Heng-Shan
authors.initials: HS
authors.lastname: Wang
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Tian
authors.forename: Jiang-Ke
authors.initials: JK
authors.lastname: Qin
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D045784:Abietanes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D045784:Abietanes; D000970:Antineoplastic Agents; D063065:Organophosphonates; C013913:dehydroabietic acid; D013890:Thiourea
keywords: Apoptosis; Cytotoxicity; Dehydroabietic acid; Thiourea; α-Aminophosphonate